Distinguishing effects of cocaine IV and SC on mesoaccumbens dopamine and serotonin release with chloral hydrate anesthesia

Abstract

The effect of i.v. cocaine (0.5 and 1.0 mg/kg) was studied on synaptic concentrations of dopamine (DA) and serotonin [5-hydroxytryptamine (5-HT)] in the mesoaccumbens nerve terminal, the nucleus accumbens (NAcc), in chloral hydrate-anesthetized, male Sprague-Dawley rats (Rattus norvegicus) with in vivo electrochemistry (voltammetry). In further in vivo voltammetric studies, the effects of SC cocaine on synaptic concentrations of DA and 5-HT were studied in the chloral hydrate-anesthetized paradigm in two neuroanatomic substrates, NAcc and mesoaccumbens somatodendrites, the ventral tegmental area (VTA-A10), in a dose-response fashion (10, 20, and 40 mg/kg) in six separate studies. Moreover, in two additional in vivo voltammetric studies, again using the chloral hydrate-anesthetized paradigm, the impulse flow blocker, gamma-butyrolactone (gamma-BL) (750 mg/kg, IP), was studied alone and in combination with SC cocaine (20 mg/kg) to determine whether or not cocaine can act by presynaptic releasing mechanisms for DA and 5-HT. The results show that IV cocaine concurrently and significantly increased DA and 5-HT release in the NAcc (p < 0.001, p < 0.0005, respectively) at both doses tested. Moreover, IV cocaine effects on DA and 5-HT release were significantly and positively correlated (p < 0.01). On the other hand, SC cocaine concurrently and significantly decreased DA and 5-HT release in NAcc (p < 0.0001) and VTA (p < 0.0001) at each separate dose tested. SC cocaine effects on DA and 5-HT release were significantly and positively correlated across dose and neuroanatomic substrate (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Real time detection of acute (IP) cocaine-enhanced dopamine and serotonin release in ventrolateral nucleus accumbens of the behaving Norway rat

“…Notably, the present results are different from the effects of (SC) cocaine on 5-HT release in vlNAcc, in the same para-digm (6), and are similar to the effect of (IV) cocaine on 5-HT-ergic release in vlNAcc, in the chloral hydrate-anesthetized rat paradigm (9). Thus, the present data demonstrate, consistent with others (37), that the route of administration for cocaine administered acutely is a crucial factor in its consequent effects.…”

“…Thus, the present data demonstrate, consistent with others (37), that the route of administration for cocaine administered acutely is a crucial factor in its consequent effects. Also, the data demonstrate that anesthesia does not significantly influence the 5-HT-erglc response to cocaine (9).…”

“…At first glance, since only the neurotransmitter DA is involved in these previous studies, acute cocaine brain reward could be analogous to the "two neuron" model of brain reward. New neurochemical data, though, implicate serotonin (5-HT) as a co-modulator mechanism for the SC and IV cocaine-induced DAergic response in A~0 neuronal circuits (6)(7)(8)(9)(10). Moreover, electrophysiological studies show a role for a 5-HT-ergic mediation in the mechanism of action of acutely administered cocaine (16,17,20,42,62).…”

“…Therefore, we examine here the effect of acute cocaine on 5-HT release concurrently with DA release in ventrolateral (vl)NAcc, on line with cocaine-induced psychostimulant behavior, when cocaine is administered by the intraperitoneal (IP) route. Importantly, the route of administration of cocaine has been shown to cause important differences in the determination of its consequent acute behavioral (37) and neurochemical effects (9). Moreover, release mechanisms are primarily addressed.…”

Methodological considerations in rat brain BOLD contrast pharmacological MRI

“…For example, a linear relationship between the time-integrated brain concentration of haloperidol and the cerebral metabolic response to this drug has been described (Pizzolato et al 1984), and dopamine and serotonin in the rat nucleus accumbens increase and decrease following i.v. and s.c. administration of cocaine, respectively (Broderick 1992). A recent study has illustrated distinct differences in the spatial distribution of cocaineinduced BOLD changes in i.c.v.-versus i.v.-treated conscious rats (Febo et al 2004).…”